bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 31, 2024
Cyclic oligonucleotide-based antiviral signaling systems (CBASS) are bacterial anti-phage defense operons that use nucleotide signals to control immune activation. Here we biochemically screen 57 diverse
Language: Английский
Microbiological Research, Journal Year: 2025, Volume and Issue: 295, P. 128107 - 128107
Published: Feb. 21, 2025
Language: Английский
Citations
3
Trends in Microbiology, Journal Year: 2024, Volume and Issue: 32(9), P. 828 - 831
Published: June 27, 2024
The study of bacterial immune systems has recently gained momentum, revealing a fascinating trend: many form large supramolecular assemblies. Here, we examine the potential mechanisms underpinning evolutionary success these structures, draw parallels to eukaryotic immunity, and offer fresh perspectives stimulate future research into immunity.
Language: Английский
Citations
7
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: Feb. 13, 2025
The astounding number of anti-phage defenses encoded by bacteria is countered an elaborate set phage counter-defenses, though their evolutionary origins are often unknown. Here, we report the discovery orphan antitoxin counter-defense element in T4-like phages that can overcome bacterial toxin-antitoxin defense system, DarTG1. DarT1 toxin, ADP-ribosyltransferase, modifies DNA to prevent replication while its cognate antitoxin, DarG1, a NADAR superfamily ADP-ribosylglycohydrolase reverses these modifications uninfected bacteria. We show some carry DarG1-like domain protein, which term anti-DarT factor (AdfN), removes ADP-ribose from during infection thereby enabling DarTG1-containing find divergent proteins unrelated likewise exhibit anti-DarTG1 activity, underscoring importance ADP-ribosylation bacterial-phage interactions, and revealing function substantial subset superfamily. Toxin-antitoxin systems make up branch immune system. Johannesman et al demonstrate have co-opted counter ADP-ribosyltransferase
Language: Английский
Citations
1
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Nov. 11, 2024
Retrons are bacterial genetic elements that encode a reverse transcriptase and, in combination with toxic effector proteins, can serve as antiphage defense systems. However, the mechanisms of action most retron effectors, and how phages evade retrons, not well understood. Here, we show some retrons other systems by producing specific tRNAs. We find expression retron-Eco7 proteins (PtuA PtuB) leads to degradation tRNA
Language: Английский
Citations
6
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown
Published: March 26, 2025
Reverse transcriptases (RTs) have well-established roles in the replication and spread of retroviruses retrotransposons. However, recent evidence suggests that RTs been conscripted by cells for diverse antiviral defense. Here we determine structures a type I-A retron, which explain how RNA, DNA, RT, HNH-nuclease four molecules an SMC-family ATPase assemble into 364 kDa complex provides phage We show phage-encoded nucleases trigger degradation retron-associated leading to disassembly retron activation HNH nuclease. The nuclease cleaves tRNA Ser , stalling protein synthesis arresting viral replication. Taken together, these data reveal paradoxical perpetuation elimination genetic parasites.
Language: Английский
Citations
0
Journal of Virology, Journal Year: 2024, Volume and Issue: 98(11)
Published: Oct. 24, 2024
ABSTRACT Toxin/antitoxin (TA) systems are present in nearly every prokaryotic genome and play the important physiological roles of phage inhibition by reducing metabolism (this includes persistence for extreme case complete cessation metabolism), genetic element stabilization, biofilm formation. TA have also been incorporated into other cell systems, such as CRISPR-Cas quorum sensing. For simplest best-studied case, proteinaceous toxins antitoxins (i.e., type II), toxin activity is masked direct binding antitoxin. A long-standing, unresolved question field how activated when bound to at nanomolar affinity. The current paradigm envisions preferential degradation antitoxin a protease, but this highly unlikely that protease cannot discriminate between because both structured. Strikingly, recent results from several studies show one likely mechanism activation conformational changes complex result release or protein trigger, phages, thermally-driven refolding dynamics.
Language: Английский
Citations
2
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: July 11, 2024
The astounding number of anti-phage defenses encoded by bacteria is countered an elaborate set phage counter-defenses, though their evolutionary origins are often unknown. Here, we discover orphan antitoxin counter-defense element in T4-like phages that can overcome the bacterial toxin-antitoxin defense system, DarTG1. DarT1 toxin, ADP-ribosyltransferase, modifies DNA to prevent replication while its cognate antitoxin, DarG1, ADP-ribosylglycohydrolase reverses these modifications uninfected bacteria. DarG1-like protein, which term anti-DarT factor NADAR (AdfN), removes ADP-ribose from during infection thereby enabling DarTG1-containing AdfN, like superfamily ADP-ribosylglycohydrolases found across domains life. We find divergent proteins unrelated likewise exhibit anti-DarTG1 activity, underscoring importance ADP-ribosylation bacterial-phage interactions, and revealing function a substantial subset superfamily.
Language: Английский
Citations
1
Cell Reports, Journal Year: 2024, Volume and Issue: 43(10), P. 114857 - 114857
Published: Oct. 1, 2024
Highlights•Phage-encoded DNA cytosine methyltransferase (Dcm) is a trigger of the retron Ec86 system•Dcm methylates stem-loop region msDNA to activate Ec86•Cryo-EM analysis reveals Ec86-effector filaments containing NAM and ADPr•The filament capable hydrolyzing NAD(P)+SummaryRetrons are class multigene antiphage defense systems typically consisting reverse transcriptase, non-coding RNA, cognate effector. Although triggers for several have been discovered recently, complete mechanism by which these detect invading phages mediate remains unclear. Here, we focus on system, elucidating its modes activation mechanisms action. We identified phage-encoded as system demonstrated that activated upon multicopy single-stranded (msDNA) methylation. further elucidated structure tripartite assembly primed Dcm nicotinamide adenine dinucleotide (NAD+). These findings provide insights into underscore an emerging theme through supramolecular complex assemblies.Graphical abstract
Language: Английский
Citations
1
Trends in Microbiology, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 1, 2024
HighlightsNoncoding RNAs (ncRNAs) have emerged as pivotal players in bacteria–phage conflicts.Many bacterial immune systems depend on ncRNAs for both structure and function.ncRNAs are key regulators of responses.Phages use to counteract defenses.AbstractThe evolutionary arms race between bacteria phages has driven the development diverse anti-phage defense mechanisms. Recent studies identified noncoding conflicts, including CRISPR-Cas, toxin–antitoxin (TA), reverse transcriptase (RT)-based defenses; however, our understanding their roles immunity is still emerging. In this review, we explore multifaceted immunity, offering insights into contributions anti-defense mechanisms, influence regulatory networks, potential biotechnological applications. Finally, highlight outstanding questions field spark future research directions.
Language: Английский
Citations
1
Cell chemical biology, Journal Year: 2024, Volume and Issue: 31(11), P. 1872 - 1873
Published: Nov. 1, 2024
Language: Английский
Citations
0